Lipid peroxidation products, such as 4-hydroxy-2-nonenal and malondialdehyde, have previously been shown to cause structural changes to proteins, including introduction of carbonyl groups into amino acid side chains. The level of carbonyl groups has proven to be a valuable measure of oxidative protein damage associated with aging, oxidative stress, and a number of diseases. Results from studies of the ability of unsaturated fatty acids to modify amino acid residues in serum albumin, glutamine synthetase, and insulin in the presence of a metal-catalyzed oxidation system [ascorbate + Fe(III)] are presented in Refsgaard, Tsai, and Stadtman, Proc. Natl. Acad. Sci. USA 97, 611 (2000). We provide evidence that hydroperoxides and/or lipid alkoxyl radicals obtained from peroxidation of polyunsaturated fatty acids react with amino acid residues. These results demonstrate that early events in lipid peroxidation contribute to protein oxidation. Studies to gain basic understanding of the interactions of protein and lipid oxidation are now continued by investigations of likely mediators of low density lipoprotein (LDL) oxidation. The lipid and protein oxidation products are characterized and the effect of oxidized LDL on cells is studied. Furthermore, the cell signaling introduced by linoleic acid oxidation products is under investigation.